TORCH: A Study of Tarceva or Chemotherapy for the Treatment of Advanced Non Small Cell Lung Cancer

NCT ID: NCT00349219

Last Updated: 2016-01-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 760 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-12-31
• Study Completion Date: 2012-06-30

Brief Summary

The purpose of this study is to compare first-line erlotinib followed at progression by second-line chemotherapy vs. first-line chemotherapy followed at progression by second-line erlotinib in the treatment of Advanced Non Small Cell Lung Cancer (NSCLC).

Detailed Description

Chemotherapy for patients affected by advanced NSCLC has demonstrated only modest improvement in survival rates over best supportive care: the prognosis of patients remains poor and the side effects are considerable. Therefore, novel agents are urgently needed for this disease. One way to improve effectiveness of therapies is to use non-chemotherapeutic agents that act on biological targets and cause fewer systemic side effects. Erlotinib(Tarceva)is a biological therapy that in recent clinical trials has shown promise in first- and second-line treatment of advanced NSCLC.

In this trial, patients will be randomized to one of two treatment strategies:

• erlotinib taken by mouth daily; and, if disease progression occurs, to be followed by chemotherapy with cisplatin and gemcitabine at standard doses for 6 cycles

OR

• chemotherapy with cisplatin and gemcitabine given intravenously at standard doses for 6 cycles; and if disease progression occurs to be followed by erlotinib taken by mouth daily

The study is conducted with the partial support of Roche, S.p.A.

Conditions

Advanced Non-Small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

erlotinib followed at progression by gemcitabine and cisplatin

Group Type: EXPERIMENTAL

erlotinib

Intervention Type: DRUG

erlotinib 150 mg taken orally daily until disease progression

cisplatin

Intervention Type: DRUG

cisplatin 80 mg/m2 IV day 1 every 3 weeks given in second-line therapy

gemcitabine

Intervention Type: DRUG

gemcitabine 1200 mg/m2 IV days 1 and 8 every 3 weeks, given in second-line

2

cisplatin and gemcitabine chemotherapy for 6 cycles, followed at progression by erlotinib

Group Type: ACTIVE_COMPARATOR

cisplatin

Intervention Type: DRUG

cisplatin 80 mg/m2 IV day 1 every 3 weeks for 6 cycles

gemcitabine

Intervention Type: DRUG

gemcitabine 1200 mg/m2 IV days 1 and 8 every 3 weeks for 6 cycles

erlotinib

Intervention Type: DRUG

erlotinib 150 mg orally taken daily as second line therapy (after disease progression on chemotherapy)

Interventions

erlotinib

erlotinib 150 mg taken orally daily until disease progression

Intervention Type: DRUG

cisplatin

cisplatin 80 mg/m2 IV day 1 every 3 weeks given in second-line therapy

Intervention Type: DRUG

gemcitabine

gemcitabine 1200 mg/m2 IV days 1 and 8 every 3 weeks, given in second-line

Intervention Type: DRUG

cisplatin

cisplatin 80 mg/m2 IV day 1 every 3 weeks for 6 cycles

Intervention Type: DRUG

gemcitabine

gemcitabine 1200 mg/m2 IV days 1 and 8 every 3 weeks for 6 cycles

Intervention Type: DRUG

erlotinib

erlotinib 150 mg orally taken daily as second line therapy (after disease progression on chemotherapy)

Intervention Type: DRUG

Other Intervention Names

Tarceva; Tarceva

Eligibility Criteria

Inclusion Criteria

• Diagnosis of cytologically or histologically confirmed non-small cell lung cancer
• Metastatic (stage IV) or locally advanced (stage IIIB, with metastasis to supraclavicular nodes or with pleural effusion).
• Both patients at first diagnosis or those with disease recurrence after former surgery are eligible.
• At least one target or non-target lesion according to RECIST criteria
• Male or female > 18 years of age (Italy upper age limit 70 years)
• ECOG PS 0 or 1
• Life expectancy of > 3 months
• Neutrophils > 1,500 mm3, platelets > 100,000 mm3, and hemoglobin > 9 g/dL
• Bilirubin level either normal or < 1.5 x ULN
• AST (SGOT) and ALT (SGPT) < 2.5 x ULN (< 5 x ULN if liver metastasis are present)
• Serum creatinine < 1.5 x ULN
• Effective contraception for both, male and female patients if the risk of conception exists
• Signed written informed consent

Exclusion Criteria

• Prior exposure to agents directed at the HER axis (e.g. gefitinib, cetuximab, trastuzumab).
• Prior chemotherapy or therapy with systemic anti-neoplastic therapy (e.g., monoclonal antibody therapy) for advanced disease. Prior surgery and/or localised irradiation is permitted. Prior neoadjuvant chemotherapy for operable disease or adjuvant chemotherapy is permitted if it did not contain gemcitabine and if at least 1 year elapsed from the end of chemotherapy and the date of relapse.
• Any unstable systemic disease (including active infections, significant cardiovascular disease or myocardial infarction within the previous year, any significant hepatic, renal or metabolic disease), metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of study medications or render the patient at high risk from treatment complications.
• Any other malignancies within past 5 years (except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer or surgically resected prostate cancer with normal PSA).
• Patients are excluded if they have brain metastasis or spinal cord compression that has not yet been definitively treated with surgery and/or radiation; previously diagnosed and treated CNS metastases or spinal cord compression without evidence of stable disease (clinically stable imaging) for at least 2 months will also cause patients to be excluded. Patients with asymptomatic CNS metastases and not requiring steroids to control symptoms can be included, even if on anti-seizure medications.
• HIV positive patients
• Any inflammatory changes of the surface of the eye at baseline
• Patients who cannot take oral medication, who require intravenous alimentation, have had prior surgical procedures affecting absorption, or have active peptic ulcer disease.
• Nursing and/or pregnant females
• Known or suspected hypersensitivity to any of the study drugs.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

San Giuseppe Moscati Hospital

OTHER

Sponsor Role: collaborator

Princess Margaret Hospital, Canada

OTHER

Sponsor Role: collaborator

University of Alberta

OTHER

Sponsor Role: collaborator

University of Campania Luigi Vanvitelli

OTHER

Sponsor Role: collaborator

National Cancer Institute, Naples

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cesare Gridelli, M.D.

Role: PRINCIPAL_INVESTIGATOR

S.G. Moscati Hospital, Avellino, Italy

Charles Butts, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada

Fortunato Ciardiello, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Second University of Naples, Italy; Chair Medical Oncology

Ronald Feld, M.D.

Role: PRINCIPAL_INVESTIGATOR

Princess Margaret Hospital, Divison of Medical Oncology, Toronto, Ontario, Canada

Ciro Gallo, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Second University of Naples, Italy; Chair Medical Statistics

Francesco Perrone, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute, Naples, Italy; Director Clinical Trials Unit

Locations

Tom Baker Cancer Centre

Calgary, Alberta, Canada

University of Alberta Cross Cancer Institute

Edmonton, Alberta, Canada

BC Cancer Agency Vancouver Island

Victoria, British Columbia, Canada

Cancer Care Mannitoba

Winnipeg, Manitoba, Canada

QE II Health Sciences Centre

Halifax, Nova Scotia, Canada

Hôpital Régional de Sudbury Regional Hospital

Greater Sudbury, Ontario, Canada

Juravinski Cancer Centre

Hamilton, Ontario, Canada

Kingston Regional Cancer Centre

Kingston, Ontario, Canada

Credit Valley Hospital

Mississauga, Ontario, Canada

Durham Regional Cancer Centre

Oshawa, Ontario, Canada

Mount Sinai Hospital

Toronto, Ontario, Canada

Princess Margaret Hospital

Toronto, Ontario, Canada

Windsor Regional Cancer Centre

Windsor, Ontario, Canada

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, Canada

McGill University Cancer Centre

Montreal, , Canada

ASL Viterbo Ospedale

Belcolle, (vt), Italy

Azienda Sanitaria S. Giuseppe Moscati

Monteforte Irpino, AV, Italy

Istituto Oncologico di Bari, U.O. di Oncologia Medica e Sperimentale

Bari, BA, Italy

Università di Chieti, Cattedra di Oncologia Medica

Chieti, CH, Italy

Humanitas Centro Catanese di Oncologia

Catania, CT, Italy

Ospedale di Gaeta

Gaeta, LT, Italy

Ospedale S. Vincenzo di Taormina

Taormina, ME, Italy

Policlinico Universitario P. Giaccone

Palermo, PA, Italy

Casa di Cura La Maddalena S.p.A., Dipartimento Oncologico

Palermo, PA, Italy

Azienda Ospedaliera V. Cervello

Palermo, PA, Italy

Azienda Ospedaliera S. Maria degli Angeli, Servizio di Oncologia

Pordenone, PN, Italy

Ospedale di Prato

Prato, PO, Italy

Ospedale Civile di Faenza, Divisione di Oncologia Medica

Faenza, RA, Italy

Istituto Regina Elena, Divisione di Oncologia Medica

Roma, Roma, Italy

Ospedale S. Luca

Vallo della Lucania, SA, Italy

Ospedale San Lazzaro

Alba, , Italy

Ospedale Cardinal Massaia

Asti, , Italy

C.R.O. Istituto Nazionale Tumori

Aviano, , Italy

Azienda Ospedaliera G. Rummo, Unità Operativa di Oncologia Medica

Benevento, , Italy

Ospedale Senatore Antonio Perrino

Brindisi, , Italy

Ospedale A. Cardarelli, divisione Medicina Interna

Campobasso, , Italy

Ospedale Ramazzini, Day Hospital Oncologico

Carpi, , Italy

A.O. Ospedale Mater Domini, Oncoematologia Università Magna Grecia

Catanzaro, , Italy

Ospedale Mariano Santo, U.O. di Oncologia Medica

Cosenza, , Italy

Ospedale S. Corce

Fano, , Italy

Azienda Ospedaliera Careggi

Florence, , Italy

Azienda Ospedaliera Morgagni Pierantoni

Forlì, , Italy

Ospedale Umberto I, U.O. di Oncologia Medica

Frosinone, , Italy

Ospedale S. Martino

Genova, , Italy

Ospedale Villa Scassi

Genova, , Italy

Ospedale S. Maria Goretti

Latina, , Italy

A.O. Vito Fazzi

Lecce, , Italy

Ospedale C. Poma

Mantova, , Italy

Policlinico Universitario G. Martino

Messina, , Italy

Casa di Cura IGEA

Milan, , Italy

Niguarda Ca' Granda

Milan, , Italy

Ospedale L. Sacco, GISCAD Oncologia, Polo Universitario

Milan, , Italy

Buon Consiglio Fatebenefratelli

Napoli, , Italy

Istituto Nazionale dei Tumori , Divisione di Oncologia Medica B

Napoli, , Italy

Ospedale Cardarelli

Napoli, , Italy

Second University of Naples

Napoli, , Italy

Università Federico II, Cattedra di Oncologia Medica

Napoli, , Italy

Divisione di Oncologia Medica, U.S.L.L. 13

Noale, , Italy

Ospedale Civile Umbero I

Nocera Inferiore, , Italy

Ospedale Civile di Nola, Reparto di Oncologia

Nola, , Italy

Istituto Oncologico Veneto

Padua, , Italy

Fondazione Salvatore Maugeri

Pavia, , Italy

Ospedale S. Salvatore

Pesaro, , Italy

Ospedale Guglielmo da Saliceto

Piacenza, , Italy

Azienda Ospedaliera S. Carol

Potenza, , Italy

Ospedale degli Infermi, U.O. Oncologia Medica

Rimini, , Italy

Ospedale S. Giovanni Calibita Fatebenefratelli, UO di Oncologia

Roma, , Italy

Azienda Ospedaliera Universitaria Arcispedal, U.O. di Oncologia Clinica

Sant'Anna Di Ferrara, , Italy

Azienda Ospedaliera Di Busto Arsizio

Saronno, , Italy

Azienda Ospedaliera Universitaria Senese

Siena, , Italy

Ospedale E. Morelli

Sondalo, , Italy

Azienda Sanitaria Locale 14

Verbania, , Italy

Ospedale S. Andrea

Vercelli, , Italy

Countries

Canada; Italy

References

Gridelli C, Ciardiello F, Gallo C, Feld R, Butts C, Gebbia V, Maione P, Morgillo F, Genestreti G, Favaretto A, Leighl N, Wierzbicki R, Cinieri S, Alam Y, Siena S, Tortora G, Felletti R, Riccardi F, Mancuso G, Rossi A, Cantile F, Tsao MS, Saieg M, da Cunha Santos G, Piccirillo MC, Di Maio M, Morabito A, Perrone F. First-line erlotinib followed by second-line cisplatin-gemcitabine chemotherapy in advanced non-small-cell lung cancer: the TORCH randomized trial. J Clin Oncol. 2012 Aug 20;30(24):3002-11. doi: 10.1200/JCO.2011.41.2056. Epub 2012 Jul 9.

Reference Type: RESULT

PMID: 22778317 (View on PubMed)

Di Maio M, Leighl NB, Gallo C, Feld R, Ciardiello F, Butts C, Maione P, Gebbia V, Morgillo F, Wierzbicki R, Favaretto A, Alam Y, Cinieri S, Siena S, Bianco R, Riccardi F, Spatafora M, Ravaioli A, Felletti R, Fregoni V, Genestreti G, Rossi A, Mancuso G, Fasano M, Morabito A, Tsao MS, Signoriello S, Perrone F, Gridelli C. Quality of life analysis of TORCH, a randomized trial testing first-line erlotinib followed by second-line cisplatin/gemcitabine chemotherapy in advanced non-small-cell lung cancer. J Thorac Oncol. 2012 Dec;7(12):1830-1844. doi: 10.1097/JTO.0b013e318275b327.

Reference Type: RESULT

PMID: 23154555 (View on PubMed)

Di Maio M, Gallo C, Leighl NB, Piccirillo MC, Daniele G, Nuzzo F, Gridelli C, Gebbia V, Ciardiello F, De Placido S, Ceribelli A, Favaretto AG, de Matteis A, Feld R, Butts C, Bryce J, Signoriello S, Morabito A, Rocco G, Perrone F. Symptomatic toxicities experienced during anticancer treatment: agreement between patient and physician reporting in three randomized trials. J Clin Oncol. 2015 Mar 10;33(8):910-5. doi: 10.1200/JCO.2014.57.9334. Epub 2015 Jan 26.

Reference Type: DERIVED

PMID: 25624439 (View on PubMed)

Other Identifiers

2005-005968-90

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

TORCH

Identifier Type: -

Identifier Source: org_study_id